Acupuncture is an ancient (over 2500 years old) therapeutic practice that originated in China and is growing in popularity in the West. However, scientific research into the basic mechanisms underlying acupuncture is relatively recent and incomplete. The purpose of the proposed study is to determine how acupuncture, with its variable treatment locations and stimulation techniques, affects human brain activity. We will accomplish this by integrating whole brain functional MRI (fMRI) with psychophysical, and physiological monitoring. Many classical acupuncture points are proposed to have multiple regulatory functions and diverse clinical effects. We propose that the neurocircuitry common to these multiple functions is comprised by the neural structures that modulate monoamine (particularly dopamine) neurotransmitter systems. Our overall hypothesis is that acupuncture will elicit a widespread brain response whose key components include neuromodulatory subcortical and brainstem structures. The limbic system, with its rich dopaminergic innervation, will play a central role in the brain's response to different acupoints and needle stimulation techniques. We will explore the central neural substrate of deqi, a unique acupuncture sensation that is considered essential to clinical efficacy in traditional Chinese acupuncture. We will also investigate the brain's response to long duration multi-acupoint needling (akin to clinical acupuncture) with model-free statistical analysis of the fMRI data, using probabilistic independent component analysis (pICA). The temporal and spatial characteristics of the independent components will be correlated with the known neurocircuitry of the monoaminergic and opioidergic systems. The goals of this study are to understand the neurobiology of acupuncture action and promote the development of this ancient healing technique into evidence-based medicine.